Effect of Foods on Basal and LPS induced NF-kappa B Activity

Abstract

The content of phytochemicals has been proposed to contribute to the beneficial effects of a diet rich in fruits and vegetables. One proposed mechanism of action of phytochemicals is down regulation of NF-kappa B activity. This transcription factor is important in inflammatory and immune responses, however aberrant activity of NF-kappa B is associated with some chronic diseases and cancers. This thesis is part of a screening project that investigates the ability of foods to modulate NF-kappa B activity by the use of a monocytic cell line stably transfected with a luciferase reporter gene coupled to a promoter of three NF-kappa B binding sites. Foods from five different food groups were tested, and both modulation of basal and LPS induced NF-kappa B activity was screened. Furthermore, potent inhibitors of LPS induced NF-kappa B activity in vitro were tested in vivo. Of the 27 extracts tested, 12 had the ability to increase basal NF-kappa B activity, and all food groups were represented with at least one item. 12 extracts inhibited LPS induced NF-kappa B activity, with red wine, green- and black tea and dark chocolate as the most potent inhibitors, all these reduced LPS induced NF-kappa B activity to less than 20 % of control. Only two extracts, unhydrosed barley and unhydrolysed oat, further increased LPS induced NF-kappa B activity. No correlation was found between the antioxidant capacity and the ability to modulate basal NF-kappa B activity, however there was a correlation between FRAP and ability to modulate LPS induced NF-kappa B activity. The most potent inhibitors of LPS induced NF-kappa B activity, were combined and tested in transgenic mice. No significant reduction in NF-kappa B activity occurred, however there was a trend towards inhibition of NF-kappa B activity in whole mice, intestine and ovaries that had been treated with the mixed extract. Based on the results in this thesis, further screening should be performed with new foods, and more investigation regarding pre-conditioning effects of foods and in vivo effects should be done.